This application is a 371 of PCT/IT99/00175, filed Jun. 17,1999
The present invention relates to a composition for the prevention and/or treatment of nervous and behavioural alterations due to anxiety states or depression.
Accordingly the composition may take the form and exert the action of a dietary supplement or of an actual medicine, depending upon the support or preventive action, or the strictly therapeutic action, which the composition is intended to exert in relation to the particular individuals it is to be used in.
Particularly the present invention relates to a composition which comprises in combination:
(a) acetyl L-carnitine or a pharmacologically acceptable salt thereof, optionally in combination with at least another xe2x80x9ccarnitinexe2x80x9d where for xe2x80x9ccarnitinexe2x80x9d is intended L-carnitine or an alkanoyl L-carnitine selected from the group comprising propionyl-L-carnitine, valeryl L-carnitine, isovaleryl L-carnitine or their pharmacologically acceptable salts; and
(b) 1,3,4,6,8,13-hexahydroxy-10,11-dimethylphenanthro[1,10,9,8-opqra]perylene-7,14-dione (hypericin) or Hypericum extract (Hypericum perforatum L., xe2x80x9cSaint-John""s-wortxe2x80x9d) comprising at least 0.3% by weight of hypericin.
The new composition can be orally, parenterally, rectally or transdermally administered both to humans and animals, as a pharmaceutical composition, dietary supplement or phytotherapy preparation.
The use of Hypericum extracts was already well known to popular medicine owing to its ability to combat a series of pathological alterations including both conditions such as depression, anxiety, insomnia, neuralgia, migraine, dyspepsia and sciatica, and inflammatory and scarring processes.
Hypericum contains numerous active components in its extracts, the most interesting of which are the naphthodianthrones, flavonoids, phloroglucinols, xanthones and a number of essential oils.
The main naphthodianthrones are hypericin, pseudohypericin and emodinanthrone.
The main flavonoids are proanthocyanidins consisting in various trimers and tetramers or polymers of catechin and epicatechin.
The phloroglucinols include prenylated derivatives of phloroglucinol, hyperpherin and perforin.
In addition to caffeic acid, coumaric acid and ferulic acid, essential oils are also present, consisting mainly in monoterpenes and sesquiterpenes.
Of all the components, hypericin is the one which more than any other has proved most interesting owing to its easy characterisation and its specificity of action.
It is, in fact, mainly to hypericin that the acknowledged anti-depressant, anxiolytic, scar-healing and antiviral effects of Hypericum extracts are to be attributed.
Recent research has demonstrated that hypericin inhibits monoamino-oxidases and cerebral serotinin reuptake, and reduces the expression of cytokines, particularly interleukin-6.
Many types of activity are exerted by the carnitines, which are generally capable of activating the processes necessary for ATP synthesis via xcex2-oxidation of fatty acids as well as of promoting stabilisation of the cell membranes against oxidative processes of both the cardiovascular and cerebral systems.
Acetyl L-carnitine improves behavioural parameters in the rat and electro-encephalographic abnormalities in elderly patients.
Neuroregeneration can also be improved by the administration of carnitines.
Surprisingly, it has now been demonstrated that a composition containing as its characterising components a combination of:
(a) acetyl L-carnitine or a phamacologically acceptable salt therof; and
(b) hypericin, is extremely effective in the prevention and/or therapeutic treatment of nervous disorders related to states of anxiety or depression, as a result of the potent synergistic effect produced by its components.
It has also been found that, advantageously, component (a) may further comprise a xe2x80x9ccarnitinexe2x80x9d selected from the group consisting of L-carnitine, propionyl L-carnitine, valeryl L-carnitine, isovaleryl L-carnitine or their pharmacologically acceptable salts or mixtures thereof, and that component (b) may consist of a hypericum (Hypericum perforatum L., xe2x80x9cSaint-John""s-wortxe2x80x9d) extract containing at least 0.3% by weight of hypericin.
The (a):(b) weight-to-weight ratio ranges from 1:0.01 to 1:1. When component (b) of the composition is present in the form of an extract of vegetable products containing it, these vegetable products include the flowers, buds and apical leaves of the Hypericum plant.